Newhouse · Neurology 2012 · Randomized, double-blind, placebo-controlled pilot trial · n=74

Nicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial.

Cited 220 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial

PubMed 22232050 · doi:10.1212/WNL.0b013e31823efcbb · record verified 2026-08-29

What was done

A 6-month, double-blind, placebo-controlled pilot randomized trial evaluated transdermal nicotine therapy (15 mg per day) in 74 nonsmoking subjects with amnestic mild cognitive impairment (MCI). Participants were randomized to nicotine (n = 39) or placebo (n = 35), and 67 completed the study (34 nicotine, 33 placebo). Primary outcome variables were attentional improvement on the Connors Continuous Performance Test (CPT), clinical improvement on clinical global impression, and safety measures. Secondary outcomes included computerized cognitive testing and patient and observer ratings.

What was found

The abstract reports directions of effect without providing exact numerical values, confidence intervals, or p-values. Transdermal nicotine produced a statistically significant improvement in the primary attentional outcome (CPT) and significant improvements in secondary measures of attention, memory, psychomotor speed, and patient/informant ratings of cognitive impairment. There was no statistically significant effect on clinician-rated global improvement. Safety and tolerability were reported as excellent.

Why it matters

This study provides pilot proof-of-concept that 6 months of transdermal nicotine is well-tolerated and can improve objective performance in attention, memory, and processing speed in nonsmoking patients with amnestic MCI.

Limits

The trial was a small pilot study (74 enrolled, 67 completed) tested at a single fixed dose (15 mg/day). The absence of a statistically significant effect on clinician-rated global impression leaves the overall clinical importance of the cognitive gains uncertain. The abstract omits exact numerical data and effect sizes.

Cited by